Phytochemical Investigation of Alnus nitida and Computational Studies of Some Selected Natural Products

Abstract

Alnus nitida is a medicinally important plant native to western Himalayas. In Pakistan it is distributed in northern areas and found abundantly in Abbottabad and Mansehra districts. Owing to the importance of the plant as a folk medicine, its wide distribution in the area and the fact that very little phytochemical work has been carried out so far on this plant, male flowers of Alnus nitida were selected for our present phytochemical investigation. In this study, we have investigated nine compounds (all new isolates of Alnus nitida) including a new one: close chain diarylheptanoid (2). They have been completely characterized by using optical rotation, ECD, UV, IR, MS, and NMR techniques. Structure of compounds 2 was validated through theoretical studies as well. The new compound 2 as well as known compounds were subjected to anticancer activity (in vitro) against cervical cancer. For this specific site cancer evaluation, HeLa cell lines and BHK-21 cell lines were used. Results showed that these compounds are potent anticancer agents. Some of them showed much higher activity compared to the reference drug, carboplatin. Computational studies have made tremendous achievements in the recent past. Conformational flexibility of dipeptides and correct assignment of isomeric compounds are challenging tasks. In the current work, we have tried to address these challenges. In the first study, the effects of intramolecular basis set superposition error and dispersion in the determination of correct lowest energy conformer of tyrosine glycine dipeptide molecule, by employing different levels of theory (B3LYP, B3LYP-D3, MP2, and M062x), are explained. The study identified the use of the best density functionals for conformationally flexible compounds especially those having aromatic moiety. In the second study, 1H-1H and 13C-1H coupling constants of possible stereoisomers of quinic acid were predicted to provide reliable assignment of chirality and positions of the hydroxy groups for quinic acids isolated from plants or the synthesized quinic acid derivatives. Analogous DFT techniques can be used to study systems similar to quinic acid such as octulosonic acids etc. In conclusion, nine isolated compounds (triterpenoid, flavonoids, open chain diarylheptanoids and close chain diarylheptanoids) with potent anticancer activity as well as conformational analysis of Tyr-Gly dipeptide and distinction of stereoisomers on the basis of coupling constants is a contribution in the field of natural product and computational chemistry.